We have made significant progress in several areas related to protein dynamics, folding, and function. (1) Protein aggregation. We have performed extensive molecular dynamics simulations of beta-amyloid fibrils based on structural models determined by Tycko and collaborators using solid-state NMR data (Buchete et al., J. Mol. Biol., 2005). We find that parallel beta-sheet structures are stable on the simulation time scale, with calculated Xray fiber diffraction patterns that compare well to experiments. Our simulations thus support and refine the structural model derived from NMR. (2) Translocation of ions and water across membrane pores. We could show that a small change in the pore diameter, as seen when comparing open and closed forms of potassium ion channels, has a dramatic effect on the ion conductivity (Peter and Hummer, Biophys. J., 2005). We could also show that structural fluctuations in molecular pores have a strong effect both on the filling of the pores with water, and the motion of water across the pores (Andreev et al., J. Chem. Phys., 2005). Simulations and calculations demonstrated that spherical hydrophobic cavities show similar hydration thermodynamics as cylindrical pores (Vaitheeswaran et al., Proc. Natl. Acad. Sci. USA, 2004). (3) Functional protein dynamics. We have developed a novel model that allows us to study slow conformational transitions of proteins (Best et al., Structure, in press, 2005). Applications to a mutant Arc repressor protein show that a conversion between helical and beta-sheet structures in the DNA binding interface proceed through local unfolding. (4) Accelerated molecular dynamics. We made significant progress in the development of new approaches to overcome the time-scale limitation in molecular simulation through path sampling (Best and Hummer, Proc. Natl. Acad. Sci. USA, 2005), the development of master equations (Hummer, New J. Phys., 2005; Sriraman et al., J. Phys. Chem. B, 2005) and temporal coarse-graining (Kevrekidis et al., AIChE J, 2004). (5) Single-molecule biophysics. By using a simple model of the folding of poly-ubiquitin under tension, we could provide an explanation for an interesting single-molecule experiment, reconciling the experiment with the large body of bulk measurements of protein folding (Best and Hummer, Science, 2005).